Human bronchial explants, pulmonary alveolar macrophages (PAM) and blood monocytes metabolically activated benzo(a)pyrene (B(A)P) and 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (7,8-diol) to ultimate mutagens. Using a human tissue- and cell-mediated mammalian mutagenesis assay these activated metabolites caused increases of ouabain resistant (Or) mutation frequency and number of sister chromatid exchanges (SCE) in the cocultivated indicator cells (Chinese hamster V-79 cells). However, benzo(e)pyrene, the weakly carcinogenic analog of B(a)P cannot be mediated by human cells to induce Or mutation of V-79 cells by B(a)P or 7,8-diol with 9-10 fold variations in their activities. The PAM preparations that could mediate more Or mutation by B(a)P also caused more mutation by 7,8-diol. These data are consistent with the hypothesis that PAM and bronchial epithelial may act in concert to metabolically activate chemical carcinogens during bronchogenic carcinogenesis. Analysis of our data concerning the induction of SCE indicates that enhancement of SCE frequency by an agent, e.g., H2O2 and trans-PT(II) does not necessarily lead to increase in mutation frequency.